Melanoma mutations modify melanocyte dynamics in co-culture with keratinocytes or fibroblasts.
J Cell Sci
; 132(24)2019 12 13.
Article
em En
| MEDLINE
| ID: mdl-31767623
ABSTRACT
Melanocytic cell interactions are integral to skin homeostasis, and affect the outcome of multiple diseases, including cutaneous pigmentation disorders and melanoma. By using automated-microscopy and machine-learning-assisted morphology analysis of primary human melanocytes in co-culture, we performed combinatorial interrogation of melanocyte genotypic variants and functional assessment of lentivirus-introduced mutations. Keratinocyte-induced melanocyte dendricity, an indicator of melanocyte differentiation, was reduced in the melanocortin 1 receptor (MC1R) R/R variant strain and by NRAS.Q61K and BRAF.V600E expression, while expression of CDK4.R24C and RAC1.P29S had no detectable effect. Time-lapse tracking of melanocytes in co-culture revealed dynamic interaction phenotypes and hyper-motile cell states that indicated that, in addition to the known role in activating mitogenic signalling, MEK-pathway-activating mutations may also allow melanocytes to escape keratinocyte control and increase their invasive potential. Expanding this combinatorial platform will identify other therapeutic target mutations and melanocyte genetic variants, as well as increase understanding of skin cell interactions.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Queratinócitos
/
Fibroblastos
/
Melanócitos
Limite:
Female
/
Humans
Idioma:
En
Revista:
J Cell Sci
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Austrália